Attempts to accelerate glucagon absorption: effects of adding a vasodilator and of injection using a 'sprinkler'...

Glucagon injected subcutaneously or intramuscularly may take up to 30 min to reverse hypoglycaemia. We investigated whether glucagon absorption could be accelerated by two manoeuvres known to enhance insulin absorption: addition of a powerful local hyperaemic agent (10 nmole alpha-calcitonin gene-related peptide; CGRP), and injection using a multihole 'sprinkler' needle. Glucagon (1 mg) given by conventional injection to six normal subjects produced peak plasma glucagon concentrations of 1.48 +/- 0.23 (SEM) ng ml-1 after 20 min and a peak glycaemic response of 7.8 +/- 0.8 mmol l-1 at 25 min. Glucagon injected with CGRP or using the sprinkler needle did not produce any significant differences in plasma glucagon or glycaemia profiles, compared with conventional injection. Further studies demonstrated that glucagon is itself a powerful vasodilator, causing a 300-500% increase in local blood flow, comparable to that induced by CGRP. Because of its intense local hyperaemic action, the absorption of subcutaneously-injected glucagon may be optimal and seems unlikely to be accelerated by pharmacological or other means.